Navdeep S. Chandel, PHD

Navdeep Chandel has made fundamental contribution to understanding the function of mitochondria. For decades, the mitochondria have been primarily viewed as biosynthetic and bioenergetic organelles generating metabolites for the production of macromolecules and ATP, respectively. He elucidated mitochondria have a third distinct role whereby they participate in cellular signaling processes through the release of reactive oxygen species (ROS) and the metabolite L-2hydroxyglutrate (L-2HG). His work has implicated the necessity of mitochondrial ROS as second messengers for multiple biological processes including hypoxic activation of HIF dependent gene transcription, cellular differentiation, and immune cell activation. He also identified that mitochondria release the metabolite L-2HG, which increases histone and DNA methylation to control hematopoietic stem cell (HSC) differentiation and regulatory T cell (Treg) function, respectively. Thus, mitochondria serve as signaling organelles. In the field of cancer, his work established that mitochondrial metabolism and ROS is necessary for tumorigenesis in vivo. Previously, the prevailing idea was that increased aerobic glycolysis (i.e. Warburg effect) was the dominant metabolic reprogramming event in cancer cells. This led to our current understanding that both aerobic glycolysis and mitochondrial metabolism are essential for tumor growth. Moreover, he found that the widely used anti-diabetic drug metformin has anti-tumor effects through inhibition of mitochondrial complex I within cancer cells. Until this finding, it was believed that metformin primarily exerts its anti-cancer effects by lowering insulin levels, a known mitogen for certain cancer cells. Finally, he wrote “Navigating Metabolism” (CSHL Press 2015), a widely utilized introductory book on metabolism.